This application is concerned with the identification and characterization of immunopathogenetic mechanisms potentially responsible for the initiation and perpetuation of hepatocellular injury in patients with viral hepatitis, type B. To this end we will examine, in chronic HBV carriers with and without chronic liver disease, the emergence and fluctuation of primary and secondary peripheral blood lymphocyte activation by hepatitis B viral antigens presented to specific antigen reactive T cells in the context of self HLA antigens using autologous fibroblast clones that contain and express the HBV genomes as stimulators. Low level T cell activation will be identified by in vitro amplification with T cell growth factor and elimination of suppressor cells. HLA restricted, viral antigen specific T cell mediated cytotoxicity will also be studied using the same clones as targets. The nature of the HBV genome in susceptible target cells will be assessed by DNA hybridization. The nature of the target antigen(s) on susceptible target cells will be assessed by blocking experiments with existing, conventional anti-viral and anti-HLA antisera and also with monoclonal anti-target cell antibodies produced during this research program. These studies will elucidate the pathogenesis of hepatocellular injury in type B viral hepatitis, which affects over 100 million chronic carriers worldwide and is associated with the debilitating sequellae of chronic liver disease and hepatocellullar carcinoma.